Purpose: Lamivudine is a potent HIV reverse transcriptase inhibitor and is commonly used in combination with other drugs to treat patients infected with HIV. A growing number of HIV- infected patients also have severe renal failure and are undergoing continuous ambulatory peritoneal dialysis (CAPD). The effect of CAPD on elimination of lamivudine is currently unknown. The purpose of this study is to evaluate the effect of CAPD on the pharmcokinetics of lamivudine in order to make dosage recommendations. Methods: Four HIV-infected patients already receiving lamivudine who also have severe renal impairment and are undergoing CAPD will be enrolled in the study. Fourteen days prior to their admission to the Duke GCRC, each patient will begin taking lamivudine from the same lot as provided by the investigators at a dose of 150 mg per day. During this period, patients will continue their CAPD regimen and all other medications as usual. The patients will then be admitted to the Duke GCRC; in the morning of day one, a pre-dose lamivudine serum sample will be drawn and then 150 mg of lamivudine will be given orally. Post-dose serum lamivudine samples will be obtained at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours. During this 24 hour period, patients will continue their usual CAPD schedule (exchanges every six hours in most cases), and a sample of dialysate will be collected from each exchange to measure lamivudine levels. In the morning of day two, a pre-dose lamivudine level will again be drawn and a 150 mg dose of lamivudine will be given orally. Again, post-dose serum lamivudine samples will be obtained at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours, but during this 24 hour period the patients will not undergo CAPD. Lamivudine levels in serum and peritoneal dialysate samples will be determined using a validated HPLC assay by personnel from Glaxo Wellcome Inc. Lamivudine serum concentrations determined pre-dose and at various times post-dose will be used to determine pharmacokinetic paramaters including the minimum serum concentration (C-min), maximum serum concentration (C-max), area under the the serum concentration versus time curve (AUC), and terminal elimination half life (t-1/2). These parameters will be calculated for each patient in the presence and absence of CAPD and may be used to determine whether or not CAPD significantly influences elimination of lamivudine. Also, for each patient, lamivudine levels will be measured in peritoneal dialysate samples throughout a 24 hour period. If the amount of lamivudine eliminated in peritoneal fluid is significant, it would suggest that dose adjustment would be necessary in patients receiving CAPD. Finally, the C-min and C-max levels around the dose of lamivudine given given on hospital day one would be expected to represent steady state levels in patients undergoing CAPD. These levels can be compared to the 50% inhibitory concentration of lamivudine and may be useful for making dosage recommendations. Results: To date, five patients have been identified in the Raleigh/Durham area who are candidates for this study. Two patients have been screened and enrolled, and one of has completed the study protocol. The study is expected be completed within the next four months. Significance: Although this is a small study, it could potentially determine if CAPD significantly influences elimination of lamivudine and could provide information to make dosage recommendations.